>Magister Scientiae - MSc / BACKGROUND: Following the historical suppression of traditional medicines in South Africa, the government published their National Health Plan in 1994 which made provision for traditional healing as an integral and recognised part of the health care system, inter alia, to establish a regulatory body for traditional medicines. Traditional medicines were included in the National Drug Policy for South Africa in 1996. A policy on traditional medicine was only drawn up in 2008 and is currently still in draft form. Some progress was made towards regulating traditional health practitioners; but very little towards regulating traditional medicines after its adoption into the National Health Plan over a decade ago. The aim of the study was to investigate how traditional medicines in South Africa can be effectively regulated with specific focus on the current status of traditional medicine regulation in South Africa; to highlight the challenges which have impeded progress towards regulating traditional medicines; and a review of regulatory strategies for traditional medicines in Ghana, India and the People’s Republic of China in an attempt to identify viable solutions to pave an effective way for regulating traditional medicines in South Africa.METHODS: The research design was exploratory and qualitative in nature following a deductive thematic analysis of data collected using a traditional literature review process. RESULTS: The delay in regulating traditional medicines in South Africa is due to a number of challenges where the most prominent is due to a lack in national priority to categorise African traditional medicine and to include it into the country’s national health system. Traditional medicines according to the World Health Organisation can be classified for inclusion into national health systems either as integrative or inclusive. Each of these inclusion strategies were presented by the chosen jurisdictions studied. An integrative health care system such as that used by China was found to be resource intensive in nature. An inclusive health care system as used in Ghana and India did not require traditional medicines as an integral part of the health care system and there were no expectations for the same requirements for regulating traditional medicines and allopathic medicines. What became apparent from the study was that irrespective of the inclusion strategy followed, there are still a number of challenges that obstruct the existence of an effective regulatory framework for traditional medicines with an overwhelming common factor of the instrumental role government play.

Chronic non-communicable diseses are a global public health challenge that continuously threatens the development and health of humans. Risk factors such as unbalanced diet-the high consumption of processed food or food from animal origin are responsible for NCDs. NCDs result in weakened immune system, making the host susceptible to opportunistic infections. Thus, the NCDs burden is most times chronic and multiple with the illness and suffering of the affected person numerous. The lack of cure for NCDs, the high cost of drugs, their high side-effects, and the emergence of multiple drug resistance has given rise to the investigation of other sources for therapeutic cure such as medicinal plants. The ethanol, n-hexane and ethyl acetate extracts of Olea europaea were analysed for their antioxidant and antimicrobial activities. The essential oil was also analysed for their chemical constituents. The n-hexane extracts of O. europaea exhibited no inhibition against all of the microorganisms tested, while the ethyl acetate and ethanol extracts exhibited inhibition, with minimum inhibitory concentration values between 0.625 mg/ml to 1.25 mg/ml. The ethanol leaf and ethyl acetate stem extracts exhibited significant activity in the inhibition of 2, 2-azinobis-(3-ethylbenzothiazolin - 6-sulfonic acid diammonium salt (ABTS) free radical, the n-hexane leaf extract had the overall significant lipid peroxidation inhibition activity, while in the inhibition of 2, 2- diphenyl-1-picrylhydrazyl radical (DPPH), the ethanol and ethyl acetate leaf extracts had strong activity. Nonanal, phytol, α-Pinene, α-Phellandrene, spatulenol and farnesol were some of chemical components identified after the GC-MS analysis of O. europaea oil. In the final part of the dissertation, Euryops brevipapposus essential oil was assessed for the antioxidant activities using free radical scavenging assays. In addition to this, the antimicrobial activities were assessed and the chemical composition was analysed using GC-MS. The essential oil demonstrated significant antioxidant activity against 2, 2-diphenyl-2-picryl-hydrazyl free radical (DPPH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and lipid peroxides with IC50 value of 0.0000000671 mg/ml, 1.05 mg/ml, and 1.170 mg/ml respectively. The essential oil also showed significant activity against all microorganisms tested with minimum inhibitory concentration (MIC) values between 0.055 mg/ml to 0.5 mg/ml. α-pinene, α- Phellandrene, germacrene D, β-pinene, trans- β.-Ocimene, bicyclogermacrene and β -Phellandrene were some of the chemical compounds identified in E. brevipapposus oil. The study has shown that E. brevipapposus and O. europaea are abundant in phytochemical compounds which were thought to be the root cause for the activities demonstrated. Therefore, these therapeutic properties observed validate and elucidate the traditional usage of the both plants in the treatment /management of diseases.

Traditional medicine, the use of plants, animals, and minerals for human health needs must be brought toa new scientific level of sustainable development in order to accommodate future global health care needs.

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Magister Scientiae - MSc / Crinum macowanii (C. macowanii) (Amaryllidacea) as authenticated by Mr. F. Weitz at the Herbarium, University of the Western cape, is widely used a traditional remedy and is thought to have therapeutic value (Fennell and van Staden 2001). The objective of this study was to determine the cardiovascular effects of the crude aqueous extract of Crinum macowanii on the rat and to determine the effect of pre-treatment drugs on Crinum macowanii in in vivo, anaesthetized normotensive, male Wistar rats (200-250 g.). / South Africa

Magister Scientiae Dentium - MSc(Dent) / The antimicrobial and antifungal efficacy of indigenous plant extracts against Streptococcus mutans , Escherichia coli and Candida albicans .Aim: To determine the antimicrobial and antifungal efficacy of indigenous plant extracts, Tamarindus Indica (T. ndica), Hibiscus sabdariffa (H. sabdaraffi), Adansonia digitata (A.digitata) and Moringa oleifera (M. oleifera) against Streptococcus mutans ( S. mutans ), Escherichia coli ( E. coli ) and Candida albicans (C. albicans) objectives:The objectives of this study were to: 1.Measure the zones of growth inhibition by T. indicia , A. digitata , M.oleifera and H. sabdariffi extracts against, S.mutans , E.coli and C.albicans . 2.Compare the size of inhibition zones of different bacteria or fungus, S. mutans ,E.coli and C. albicans, around the same plant extract.3.Compare the size of inhibition zones for the same bacteria in different plant extracts T.indicia ,A.digitata H.sabdariffi and M.oleifera Methodology .The antimicrobial and antifungal effect of the ethanolic extracts of T. indica , H.sabdariffa, A.digitata and M.oleifera was performed using the disc diffusion method against S. mutans ,E.coli and C.albicans. The antibacterial and antifungal activity of the plants was determined by measuring the diameter of the inhibition zones. esults and conclusion: The results showed that.T.indica and H.sabdariffa ethanolic extracts have an antibacterial effect against S.mutans and E.coli.However, H.sabdariffi showed a significantly higher antibacterial effect against E.coli and S.mutans, with a range of 14.50mm to 12.01mm and 16.41 mm to 14.39 mm compared to T.indica ,with a range of 11.41 mm to 7.04mm and 6.88mm to 10.40mm, respectively.Furthermore, the statistical multiple pairwise test (Conover Iman procedure/Two -tailed test) omputed that the effect of H.sabdariffi is significantly (critical value >7.229) greater for the G ram positive S.mutans than the G ram negative E.coli.On the other hand,T.indica showed a similar antibacterial effect against S.mutans and E.coli,respectively.In contrast, M. oleifera and A.digitata ethanolic plant extracts showed no antibacterial effect against E.coli and S.mutans. All the indigenous plants tested, T.indica ,H.sabdariffa, M. oleifera and A.digitata had no antifungal activity on C.albicans

Magister Pharmaceuticae - MPharm / Evaluation of the antinociceptive, anti-inflammatory and antipyretic activities of Ruta graveolens L. in mice and rats FIRDOWS LOONAT M. Pharm. Pharmaceutical Sciences thesis: School of Pharmacy, University of the Western Cape Ruta graveolens (Rutaceae) L. is a medicinal plant that is commonly used to manage and treat essential events such as pain, inflammation and fever. Despite its popularity, particularly as a medicinal plant in the Calvinia district and Bredasdorp region of South Africa, scientific data to substantiate its widespread traditional use and the possible mechanisms of action for this plant species is lacking. Therefore, the objectives of this study were: to scientifically evaluate and validate the antinociceptive, anti-inflammatory and antipyretic activities of Ruta graveolens using the acetic-acid writhing test and hot-plate test, the carrageenan rat paw oedema test, and the E. coli-induced pyrexia test, respectively; to investigate the possible mechanisms of the antinociceptive, anti-inflammatory and antipyretic activities of the plant using interaction studies; to determine some secondary metabolites present in the plant species using standard phytochemical analytical procedures; to characterise the plant species using HPLC techniques; and to determine the safety profile of the plant species using an acute toxicity study.Three percent (3 %) acetic acid (0.25 ml, i.p.) produced a substantial number of writhes in mice. The leaf methanol extract of Ruta graveolens (100 mg/kg, i.p.) significantly reduced the number of writhes induced by 3 % acetic acid (0.25 ml, i.p.). R. graveolens (100 mg/kg,i.p.) produced 54 % inhibition of 3 % acetic acid-induced writhes. Indomethacin (20 mg/kg,i.p.) and paracetamol (500 mg/kg, i.p.) significantly reduced the number of 3 % acetic acidinduced writhes. Indomethacin (20 mg/kg, i.p.) and paracetamol (500 mg/kg, i.p.) produced 57 % and 80 % inhibition of 3 % acetic acid-induced writhes, respectively. R. graveolens (25– 50 mg/kg, i.p. and 200 – 400 mg/kg, i.p.) and indomethacin (10 mg/kg, i.p.) did not significantly reduce the number of writhes induced by 3 % acetic acid. However, combined therapy of the leaf methanol extract of R. graveolens (25 mg/kg, i.p.) and indomethacin (10 mg/kg, i.p.) significantly reduced the number of 3 % acetic acid-induced writhes. The combined therapy of the lowest and sub-effective doses of the leaf methanol extract of R. graveolens (25 mg/kg, i.p.) and indomethacin (10 mg/kg, i.p.) produced 59 % inhibition of the writhes elicited by 3 % acetic acid. The leaf methanol extract of R. graveolens (50 – 400 mg/kg, i.p.) greatly delayed the reaction time in mice to thermal stimulation produced with hot-plate. 50 – 400 mg/kg (i.p.) of the leaf methanol extract of R. graveolens significantly antagonised rat paw oedema induced by 1 % carrageenan (0.1 ml, subplantar) over the 4 h period of testing. In addition, indomethacin (10 mg/kg, i.p.) significantly antagonised 1 % carrageenan-induced rat paw oedema. R. graveolens (25 mg/kg, i.p.) and indomethacin (2mg/kg, i.p.) given separately did not significantly alter rat paw oedema induced by 1 % carrageenan. However, combined therapy of the leaf methanol extract of R. graveolens (25 mg/kg, i.p.) and indomethacin (2 mg/kg, i.p.) significantly reduced 1 % carrageenan-induced rat paw oedema. The leaf methanol extract of R. graveolens (400 mg/kg, i.p.) significantly reduced the mean rectal temperature of normothermic rats. Ruta graveolens (100 – 400 mg/kg, i.p.) significantly reduced pyrexia induced by E. coli (50 μg/kg, i.m.) over the 5 h period of testing. In addition, pentoxifylline (50 mg/kg, i.p.) significantly reduced E. coliinduced pyrexia. Ruta graveolens (25 – 50 mg/kg, i.p.), paracetamol (500 mg/kg, i.p.) and pentoxifylline (10 mg/kg, i.p.) did not significantly reduce pyrexia induced by E. coli.However, combined therapy of the leaf methanol extract of R. graveolens (25 mg/kg, i.p.)and pentoxifylline (10 mg/kg, i.p.) significantly reduced E. coli (50 μg/kg, i.m.)-induced pyrexia.The phytochemical studies of the powdered leaves of Ruta graveolens indicated the presence of alkaloids, cardiac glycosides, flavonoids, saponins, tannins and triterpene steroids. The HPLC fingerprint indicated characteristic peaks at the following retention times; 1.654 min,2.271 min, 2.403 min, 4.705 min and 7.691 min. The LD50 obtained for Ruta graveolens after oral administration was probably greater than 4000 mg/kg which shows that the plant extract is non-toxic to mice.In conclusion, the data obtained indicate that Ruta graveolens possesses antinociceptive, antiinflammatory and antipyretic activities. Since prostaglandins have been shown to mediate acetic acid-induced writhes, prostaglandins, histamine, serotonin, capsaicin and bradykinin implicated in carrageenan-induced rat paw oedema, and tumor necrosis factor-α (TNF-α) implicated in E.coli-induced pyrexia, it is possible that R. graveolens may be producing its antinociceptive, anti-inflammatory and antipyretic activities by affecting these chemical mediators. The data obtained also justify the use of the plant species by traditional medicine practitioners for the treatment of painful and inflammatory conditions, and pyrexia.

In Africa, the importance of medicinal plants in folklore medicine and their contribution to primary healthcare is well recognized. Across the continent, local herbal mixtures still provide the only therapeutic option for about 80% of the population. The vast floral diversity and the intrinsic ethnobotanical knowledge has been the backbone of localized traditional herbal medical practices. In Africa, an estimated 5400 of the 60000 described plant taxa possess over 16300 therapeutic uses. Similarly, with a therapeutic flora comprising of approximately 650 species, herbal medical practitioners in South Africa, make use of a plethora of plants to treat different human diseases and infections. Over the years, studies have identified numerous plant species with potential against chronic metabolic diseases including type 2 diabetes mellitus (T2DM). Globally, the incidence and prevalence of T2DM have reached epidemic proportions affecting people of all ages, nationalities and ethnicity. Considered the fourth leading cause of deaths by disease, T2DM is a global health crisis with an estimated diagnosis and mortality frequency of 1 every 5 seconds and 1 every 7 seconds respectively. Though the exact pathophysiology of T2DM is not entirely understood, initial peripheral insulin resistance in adipose tissue, liver, and skeletal muscle with subsequent pancreatic β-cell dysfunction resulting from an attempt to compensate for insulin resistance is a common feature of the disease. The current approach to treating T2DM is the use of oral antidiabetic agents (OAAs), insulin, and incretin-based drugs in an attempt to achieve glycaemic control and maintain glucose homeostasis. However, conventional anti-T2DM drugs have been shown to have limited efficacies and serious adverse effects. Hence, the need for newer, more efficacious and safer anti-T2DM agents. Sutherlandia frutescens subsp. microphylla is a flowering shrub of the pea family (Fabaceae/Leguminaceae) found mainly in the Western Cape and Karoo regions of Southern Africa. Concoctions of various parts of the plant are used in the management of different ailments including T2DM. However, despite extensive biological and pharmacological studies, few analyses exist of the chemical constituents of S. frutescens and no Triple Time of Flight Liquid Chromatography with Mass Spectrometry (Triple TOF LC/MS/MS) analysis has been performed. The initial aim of this study was to investigate the phytochemical profile of hot aqueous, cold aqueous, 80% ethanolic, 100% ethanolic, 80% methanolic and 100% methanolic extracts of a single source S. frutescens plant material using colorimetric and spectrophotometric analysis. The hot aqueous extractant was found to be the best extractant for S. frutescens, yielding 1.99 g of crude extract from 16 g fresh powdered plant material. This data suggests that application of heat and water as the extractant (hot aqueous) could play a vital role in extraction of bioactive compounds from S. frutescens and also justifies the traditional use of a tea infusion of S. frutescens. Colorimetric analysis revealed the presence of flavonoids, flavonols, tannins, and phenols in all extracts with varying intensity. The organic extracts 100% methanol, 80% and 100% ethanol exhibited high color intensity (+++) for flavonoids and flavonols respectively, while all the extracts exhibited a moderate color intensity (++) for tannins and phenols. Spectrophotometric analysis of S. frutescens extracts revealed that all the organic extracts contained a significantly higher concentration (in mg/g of extract) of flavonols and tannins when compared to the aqueous extracts. All extracts contained approximately equal levels of phenols. These data confirm the presence of all four groups of bioactive phytocompounds in the S. frutescens extracts used in this study, and also confirm that different solvent extractants possess the capability to differentially extract specific groups of phytocompounds. in individual extracts. Further comparison of these compounds with online databases of anti-diabetic phytocompounds led to the preliminary identification of 10 possible anti-diabetic compounds; α-Pinene, Limonene, Sabinene, Carvone, Myricetin, Rutin, Stigmasterol, Emodin, Sarpagine and Hypoglycin B in crude and solid phase extraction (SPE) fractions of S. frutesecens. Furthermore, using two hepatic cell lines (Chang and HepG2) as an in-vtro model system, the anti-T2DM properties of crude aqueous and organic extracts of S. frutescents was investigated and compared. Both aqueous and organic extracts of S. frutescens were found to decrease gluconeogenesis, increase glucose uptake and decrease lipid accumulation (Triacylglycerol, Diacylglycerol, and Monoacylglycerol) in Chang and HepG2 hepatic cell cultures made insulin resistant (IR) following exposure to high concentration of insulin and fructose. Using real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the aqueous and organic extracts of S. frutescens were confirmed to regulate the expression of Vesicle-associated membrane protein 3 (VAMP3), Mitogen-activated protein kinase 8 (MAPK8), and Insulin receptor substrate 1 (IRS1) in insulin resistant hepatic cells. IR-mediated downregulation of VAMP3, MAPK8, and IRS1 mRNA in IR HepG2 hepatic cell cultures was reversed in the presence of aqueous and organic extracts of S. frutescens. The hot aqueous extract displayed the highest activity in all the assays, while all the organic extracts displayed similar potency. In conclusion, this study reports that aqueous and organic extracts of S. frutescens possess numerous anti-diabetic compounds that can be further investigated for the development of new, more efficacious and less toxic anti-diabetic agents. The presence of multiple compounds in a single extract does suggest a synergistic or combinatorial therapeutic effect. These findings support the burgeoning body of in-vivo and in-vitro literature evidence on the anti-diabetic properties of S. frutescens and its use in folklore medicine.

The incidence of Type 2 Diabetes Mellittus (T2DM) is increasing world wide. In Africa the limited access to health care and the insidious course of the disease lead to more severe illness and diabetic complications. There is a need to find alternative approaches to treatment and prevention that address the problems and needs of Africa. Sutherlandia frutescens (S.frutescens) is a traditional herbal plant with known anti-diabetic properties, the precise mechanism of action of S.frutescens is not known. In order to develop new approaches for treatment and prevention of T2DM the pathophysiology of T2DM must be understood. T2DM is the final outcome of a multi-organ disease characterized by early defects in muscle, adipocytes, hepatocytes and pancreatic β-cells. In this study the role of the liver was investigated because of its central role in glucose and lipid metabolism. It is hard to differentiate between all the influences in an in vivo model, so the aim of this study was to develop an in vitro model of T2DM in Chang liver cells and to determine if S.frutescens can reverse the state of insulin resistance in this model. Different culture media conditions were screened to identify a method that can be used as the T2DM model in Chang liver cells. Serum free medium (MCBD-201) supplemented with human diabetic serum, (2.5%-10%), high insulin concentrations (0.1μM-1μM), high fructose concentrations (1-10mM). and a combination of high insulin and high fructose was used for this screening. Chang liver cells cultured in MCBD-201 medium supplemented with 1mM fructose and 0.1μM insulin showed reduced glucose uptake and increased lipid accumulation. The effect of two S.frutescens extracts, two anti-diabetic drugs, metformin and ciglitazone, and a hypolipidemic drug ciprofibrate were determined and shown to increase glucose uptake and reduce lipid accumulation. It was postulated that exposing the cells to excess nutrients in the form of high fructose would stimulate the cells to become adipogenic and accumulate lipids, which would interfere with the glucose uptake and induce insulin resistance. Gene expression of PPARγ, PPARα, and SREBP-1 transcription factors regulating lipid metabolism was determined in Chang liver cells cultured in insulin resistance inducing medium over a 48 hour time course. The expression of PPARγ, known to stimulate adipogenesis was increased after 6, 24 and 48 hours of exposure (P(H1)<0.0001). The expression of PPARα, known to stimulate β-oxidation expression, was significantly decreased after 24 hours of exposure (P(H1)<0.0001). The presence of the plant extracts in the insulin resistance inducing media protect against this increase in adipogenesis and decrease in β-oxidation after 48 hours of exposure by increasing PPARα expression and decreasing PPARγ expression. A PCR Array was performed which identified 32 more potential molecular targets of S.frutescens. Five of the 32 targets identified with the PCR Array were validated using qRT-PCR. These genes play a role in lipid and glucose metabolism and protection against oxidative stress and inflammation. In summary a cellular model of insulin resistace in hepatocytes has been established and the capacity of S.frutescens to reverse this process has been demonstrated by acting as a dual PPARγ/α agonist. New genes have been identified in the development of insulin resistance and as targets of S.frutescens.

A follow-up of traditional medicinal plants uses is an important tool in highlighting their therapeutic potentials, as they have been found to be a source of a wide range of bioactive compounds that can be used as base compounds for new pharmaceutical drugs. This study therefore focuses on assessing the anti-Listerial properties of the seeds of Garcinia kola (Heckel) plant, which is a traditional medicinal plant of west and central African origin, and was and is still used to traditionally treat several ailments. Four different solvents crude extracts of the seeds were assessed for their anti-Listerial activities in-vitro, against a panel of 42 Listeria bacteria, which included Listeria monocytogenes, Listeria ivanovii and Listeria grayi species. At 10 mg/ml concentration the aqueous extract had activity against 29% of the test isolates while the other three crude extracts namely dichloromethane, n-hexane and the methanol extracts had activity against 45% of the test bacteria. The minimum inhibitory concentration (MIC) ranges of the extracts were 0.079-0.313 mg/ml for the dichloromethane extract; 0.079-0.625 mg/ml for the n-hexane extract; 0.157-0.625 mg/ml for the methanol extract; and 10->10 mg/ml for the aqueous extract. The minimum bactericidal concentration (MBC) ranges of the extracts were 0.625–10 mg/ml for both the n-hexane and the dichloromethane extract; 5-10 mg/ml for the methanol extract; and those for the aqueous extract were above 10 mg/ml against all the susceptible Listeria isolates. The rate of kill analysis was then determined for the three most active crude extracts that is excluding the aqueous extract and it was assessed against four representative Listeria species namely L. monocytogenes (LAL 8), L. grayi (LAL 15), L. ivanovii (LEL 30) and L. ivanovii (LEL 18). All the three extracts showed a general trend of being concentration and time dependent in their rate of kill profiles such that most bacteria cells were killed at the highest test concentration of 4× MIC value after the maximum exposure time of 2 h. The n-hexane, dichloromethane and methanol extracts were bactericidal against 4, 3 and 1 isolates out of the four test Listeria isolates respectively.